Last Updated: September 24, 2026

Details for Patent: 4,938,763


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Summary for Patent: 4,938,763
Title:Biodegradable in-situ forming implants and methods of producing the same
Abstract:A biodegradable polymer is provided for use in providing syringeable, in-situ forming, solid biodegradable implants for animals. The polymer is placed into the animal in liquid form and cures to form the implant in-situ. A thermoplastic system to form said implant comprises the steps of dissolving a non-reactive polymer in biocompatible solvent to form a liquid, placing the liquid within the animal, and allowing the solvent to dissipate to produce the implant. An alternative, thermosetting system comprises mixing together effective amounts of a liquid acrylic ester terminated, biodegradable prepolymer and a curing agent, placing the liquid mixture within an animal and allowing the prepolymer to cure to form the implant. Both systems provide a syringeable, solid biodegradable delivery system by the addition of an effective level of biologically active agent to the liquid before injection into the body.
Inventor(s):Richard L. Dunn, James P. English, Donald R. Cowsar, David P. Vanderbilt
Assignee: Tolmar Therapeutics Inc
Application Number:US07/252,645
Patent Claim Types:
see list of patent claims
Use; Delivery; Device;
Patent landscape, scope, and claims:

United States Patent 4,938,763: Claim Scope, Expiration, and In-Situ Drug-Delivery Patent Landscape

U.S. Patent No. 4,938,763 is a foundational platform patent for injectable, in-situ forming implants. Its claims cover dissolving a water-insoluble polymer in a biocompatible solvent, placing the liquid in a living body, and allowing solvent dissipation to create a solid implant. Dependent claims narrow the platform to binary solvents, needle delivery, biodegradable polymers, periodontal implants, tetracycline compounds, and benzophenanthridine alkaloids.

The patent issued July 3, 1990, and its enforceable term has expired. Assuming the standard pre-Uruguay Round Agreement patent term applicable to the patent, the term ended July 3, 2007, absent an earlier terminal disclaimer or other unusual limitation. The patent therefore presents no current blocking right. Its commercial importance remains substantial because later patents and products built around the same Atrigel-type technology may have protected specific formulations, drugs, dosage forms, manufacturing processes, or clinical uses.

What does U.S. Patent 4,938,763 protect?

The core invention is an injectable liquid that converts into a solid implant after administration. The conversion occurs because the solvent leaves the formulation, principally through diffusion into surrounding body fluids, while the polymer precipitates or solidifies.

Claim group Subject matter Scope
Claims 1, 14-16 In-situ implant formed from polymer and solvent Broad platform claims
Claims 2 Binary solvent system Requires a polymer solvent and a nonsolvent
Claims 3-4 Needle delivery and selected polymers/solvents Injectable biodegradable formulation
Claims 5, 8-12 Drug-loaded implants Covers controlled release of specified agents
Claims 6-7 Periodontal pocket and selected drugs Periodontal application
Claims 13 and 19 Implant products made by the claimed method Product-by-process claims
Claims 17-18 Solvent Markush groups Lists specific solvent classes and mixtures

Claim 1 is the principal platform claim. It requires four functional elements:

  1. A non-reactive, water-insoluble polymer.
  2. A biocompatible, water-soluble solvent.
  3. Placement of the polymer solution inside a living body.
  4. Solvent dissipation that produces a solid implant.

The claim does not require the polymer to be biodegradable, contain a drug, be delivered through a needle, or be used for periodontal treatment. Those limitations appear in later claims.

How broad is independent claim 1?

Claim 1 is technologically broad but legally constrained by its required sequence and material characteristics.

Polymer limitations

The polymer must be water-insoluble and non-reactive. The claim does not expressly require biodegradability. A formulation using a nondegradable polymer could potentially fall within claim 1 if the other limitations were satisfied.

Claims 14-16 narrow the polymer scope. Claim 15 lists:

  • Polylactides
  • Polyglycolides
  • Polycaprolactones
  • Polydioxanones
  • Polycarbonates
  • Polyhydroxybutyrates
  • Polyalkylene oxalates
  • Polyanhydrides
  • Polyamides
  • Polyesteramides
  • Polyurethanes
  • Polyacetals
  • Polyketals
  • Polyorthocarbonates
  • Polyphosphazenes
  • Polyhydroxyvalerates
  • Polyalkylene succinates
  • Poly(malic acid)
  • Poly(amino acids)
  • Chitin
  • Chitosan
  • Polyorthoesters
  • Copolymers, terpolymers, combinations, and mixtures

Claim 16 focuses on polylactides, polycaprolactones, and copolymers with glycolide. This claim is particularly relevant to later poly(lactide-co-glycolide), or PLGA, delivery systems.

Solvent limitations

The solvent must be biocompatible and water-soluble under claim 1. Claim 17 lists:

  • N-methyl-2-pyrrolidone
  • 2-pyrrolidone
  • Ethanol
  • Propylene glycol
  • Acetone
  • Ethyl acetate
  • Methyl acetate
  • Methyl ethyl ketone
  • Dimethylformamide
  • Dimethyl sulfoxide
  • Tetrahydrofuran
  • Caprolactam
  • Decylmethylsulfoxide
  • Oleic acid
  • 1-dodecylazacycloheptan-2-one
  • Combinations and mixtures

Claim 18 narrows the solvent set to N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, acetone, and mixtures.

A potential claim-construction issue is that several solvents listed in claims 17-18 may not ordinarily be characterized as water-soluble in the same manner. The specification and prosecution history would be important in determining whether “water-soluble” means fully miscible with water, soluble at a meaningful concentration, or functionally capable of leaving the implant through body fluids.

What does claim 2 add to the patent scope?

Claim 2 covers a binary solvent system. The first solvent dissolves the polymer. The second solvent does not dissolve the polymer. The two solvents are mixed at a ratio at which the polymer remains soluble.

After administration, the second solvent-to-first-solvent ratio increases as the first solvent dissipates or diffuses more rapidly. Polymer precipitation follows.

This limitation targets phase-inversion or solvent-exchange formulations. A competing formulation could avoid claim 2 while still potentially implicating claim 1 if it uses a single polymer solvent that dissipates and produces a solid implant.

The binary-solvent limitation creates several technical design-around paths:

  • Use a single solvent.
  • Use a polymer melt rather than a polymer solution.
  • Use a chemically crosslinking system.
  • Use an in-situ polymerization reaction.
  • Use a preformed microparticle suspension.
  • Use a nonaqueous solvent system that does not satisfy the claimed water-solubility characteristics.
  • Use a formulation in which solidification results from chemical reaction rather than solvent dissipation.

Those alternatives may implicate later patents even if they avoid the expired patent.

What drug-delivery embodiments are covered?

Claims 5-12 extend the platform to drug-loaded implants. The drug is released by diffusion, polymer erosion, or both as the implant biodegrades.

The expressly identified active agents are:

Claim Active agent
Claim 7 Benzophenanthridine alkaloid or tetracycline
Claim 8 Benzophenanthridine alkaloid
Claim 9 Sanguinarine chloride
Claim 10 Ethoxydihydrosanguinarine
Claim 11 Tetracycline base
Claim 12 Tetracycline hydrochloride

Claim 6 specifies formation in a periodontal pocket. The periodontal claims are narrower than the general drug-delivery claims because they require the anatomical site.

The claims cover more than the commercial product associated with a particular doxycycline formulation. Claims 5 and 8-12 use broader drug categories and are not limited to doxycycline, dose, concentration, release rate, particle size, polymer molecular weight, or administration schedule.

What is the relationship to Atridox and Atrigel technology?

The patent is associated with the early intellectual-property foundation for in-situ forming biodegradable implant technology commonly known as Atrigel-type delivery. Atridox is a periodontal product containing doxycycline hyclate and a biodegradable polymer formulation. FDA labeling identifies Atridox as a subgingival product for localized treatment of adult periodontitis (U.S. Food and Drug Administration, n.d.-a).

The supplied claims are broader than a doxycycline periodontal product because they cover:

  • Multiple biodegradable polymers.
  • Multiple solvent systems.
  • Multiple active agents.
  • General body implantation.
  • Needle administration.
  • Drug-free implants.
  • Periodontal and non-periodontal uses.

Later commercial products would generally require separate analysis of later patents directed to:

  • Doxycycline or other active-ingredient formulations.
  • Polymer molecular weight and composition.
  • Syringe and delivery systems.
  • Product stability.
  • Release kinetics.
  • Periodontal dosing.
  • Manufacturing and filling methods.
  • Combination-product regulatory features.

When did U.S. Patent 4,938,763 lose exclusivity?

U.S. Patent 4,938,763 issued on July 3, 1990. For a U.S. application filed before June 8, 1995, the governing term generally was 17 years from grant, subject to statutory adjustments and disclaimers. On that basis, the patent expired on July 3, 2007.

Event Date
Patent grant July 3, 1990
Standard pre-1995 term 17 years from grant
Expected expiration July 3, 2007
Current status Expired
Current Paragraph IV relevance None for this patent

The patent cannot currently support an injunction against a generic, 505(b)(2) applicant, medical-device company, or drug-delivery competitor. A later patent claiming a narrower formulation may still be enforceable independently.

What is the Orange Book status of U.S. Patent 4,938,763?

U.S. Patent 4,938,763 should not be treated as a current Orange Book barrier. Its 2007 expiration predates the present commercial life of many in-situ forming products and removes it as a live patent-exclusivity asset.

Orange Book listing is product-specific. A patent is ordinarily relevant only if it claims the approved drug, a formulation or composition of the approved drug, or an approved method of use, subject to FDA listing rules. A broad, expired platform patent does not create current Orange Book exclusivity for every product using a similar delivery concept.

For Atridox, the relevant regulatory record is the NDA and any product-specific patents listed by the sponsor or approved holder. The expired patent should not be counted as a currently listed, enforceable Atridox patent without a product-specific historical listing record. The FDA’s Orange Book provides the controlling product-level source (U.S. Food and Drug Administration, n.d.-b).

Are there Paragraph IV challenges to this patent?

No current Paragraph IV challenge can create a launch risk based on U.S. Patent 4,938,763 because the patent has expired.

A Paragraph IV certification addresses a patent listed for an approved drug in the Orange Book. A generic applicant could not be required to wait for expiration of this patent today. Any modern challenge involving an Atrigel-type or periodontal product would likely target later patents covering the active ingredient, formulation, dosage form, device, method of use, or manufacturing process.

The relevant launch paths would likely include:

  • Abbreviated New Drug Application, if the product can demonstrate pharmaceutical equivalence and bioequivalence.
  • 505(b)(2) application, if the product uses a different formulation, delivery system, or clinical justification.
  • Medical-device or combination-product requirements, depending on the product design.
  • New drug application, if the product is materially different or lacks a suitable reference product.

Does the patent create biosimilar risk?

No. U.S. Patent 4,938,763 claims polymeric implants and drug-delivery methods, not a biologic molecule. It does not create biosimilar risk under the Biologics Price Competition and Innovation Act.

The competitive risk is instead associated with generic drugs, 505(b)(2) products, drug-device combinations, and alternative local-delivery systems. Products containing proteins or peptides could use a similar implant platform, but their regulatory pathway would be governed by the active biologic and the applicable FDA biologics framework, not by this patent.

How strong is the patent estate?

Historical strength

The patent had high platform breadth when unexpired. Claim 1 reached the central concept of converting an injectable polymer solution into an implant inside the body. Claims 14-18 provided substantial material and solvent coverage, while claims 5-12 addressed drug release and periodontal use.

The strongest historical claim characteristics were:

  • Broad method architecture.
  • Multiple polymer classes.
  • Multiple solvent classes.
  • Coverage of drug-loaded and drug-free implants.
  • Coverage of needle delivery.
  • Coverage of localized periodontal treatment.

Current strength

Current enforceability is zero because the patent expired. Its residual value is technical and historical:

  • It may be prior art against later patent applications.
  • It may constrain the validity of broad later claims.
  • It may explain the development history of Atrigel-type products.
  • It may support freedom-to-operate arguments against claims that merely restate the same platform concept.

The patent does not provide a current royalty position or exclusionary right.

What later patents create the principal commercial risk?

The main risk is not this patent. It is the later patent estate around particular products and implementations.

Later patent category Typical protected subject matter Commercial impact
Active-ingredient formulation Doxycycline, leuprolide, peptides, or other agents in the polymer matrix May block a specific product
Polymer formulation PLGA ratio, molecular weight, end groups, concentration Can protect release and degradation profiles
Solvent system NMP, pyrrolidone, alcohol, cosolvent ratios May cover a commercial formulation
Delivery device Dual-chamber syringe, mixing system, cannula, needle Can create device or combination-product barriers
Release profile Burst control, sustained release, local concentration May support method or formulation claims
Manufacturing Mixing, filling, sterilization, storage, packaging Can create process and supply-chain barriers
Method of use Periodontitis, oncology, hormone therapy, pain May affect labeling and induced-infringement risk

A complete current freedom-to-operate review must separate expired platform claims from unexpired continuation, divisional, continuation-in-part, foreign, and product-specific patents.

What geographic coverage remains?

U.S. Patent 4,938,763 has no current U.S. exclusionary effect. Foreign counterparts, if any, would have expired under the national patent term applicable in each jurisdiction or lapsed earlier for failure to pay maintenance fees.

The commercial assessment should distinguish:

  • United States patent expiry.
  • European Patent Convention validation and expiry.
  • Japan, Canada, Australia, and other national rights.
  • Patent term extensions.
  • Supplementary protection certificates.
  • Pediatric extensions.
  • Local regulatory exclusivity.

A U.S. expiry does not establish worldwide freedom to operate, although a patent issued in 1990 would ordinarily also be outside its normal enforceable term in major jurisdictions.

What licensing deals are associated with the technology?

The patent itself does not establish the terms of any licensing agreement. Commercial use of the platform has involved corporate transactions and product-specific rights separate from the patent document. Assignment records, SEC filings, license agreements, and FDA sponsor records are required to map ownership and commercialization rights.

For transaction analysis, the relevant asset is likely a patent family rather than U.S. Patent 4,938,763 alone. A license review should include:

  • Continuations and divisionals.
  • Improvements to the polymer-solvent system.
  • Product-specific drug claims.
  • Device patents.
  • Know-how and manufacturing rights.
  • Territory and field-of-use restrictions.
  • Royalty terms and sublicensing rights.
  • Patent prosecution and enforcement control.

What generic launch scenarios exist?

The expired patent permits several competitive routes:

  1. A generic or 505(b)(2) product can use the same broad in-situ precipitation concept without infringing this patent.
  2. A competitor can use a different polymer-solvent combination.
  3. A competitor can change the active ingredient, polymer ratio, dosage form, or delivery device.
  4. A competitor can pursue a preformed implant, microsphere, injectable gel, or alternative local-delivery system.
  5. A sponsor can challenge later Orange Book patents through Paragraph IV certification.

The principal barriers would be later patents, FDA requirements, manufacturing validation, product stability, syringe performance, sterility, and clinical comparability.

Key Takeaways

  • U.S. Patent 4,938,763 covers the basic in-situ forming implant platform.
  • Claim 1 is broad and does not require biodegradability or a drug.
  • Claims 2-4 focus on binary solvents, needle delivery, lactide polymers, and selected nonsolvents.
  • Claims 5-12 cover drug-loaded biodegradable implants, including tetracyclines and benzophenanthridine alkaloids.
  • Claims 14-18 provide detailed polymer and solvent Markush coverage.
  • The patent expired around July 3, 2007, based on the standard pre-1995 17-year patent term.
  • It creates no current Orange Book, Paragraph IV, biosimilar, or injunction risk.
  • Current freedom-to-operate risk lies in later patents covering commercial formulations, active ingredients, devices, manufacturing, and methods of use.
  • Atridox and related Atrigel-type products require product-specific analysis separate from this expired platform patent.

FAQs

Can a company use the Atrigel concept after U.S. Patent 4,938,763 expired?

Yes. The expired patent no longer prevents use of the claimed platform. Later patents and regulatory requirements may still restrict a particular product.

Does claim 19 provide an independent product patent?

Claim 19 is a product-by-process claim directed to a biodegradable implant produced according to claim 1. Its enforceability historically depended on both the product characteristics and the claimed manufacturing method. It is expired with the patent.

Does using N-methyl-2-pyrrolidone avoid infringement of this patent?

No. N-methyl-2-pyrrolidone is expressly listed in claims 17 and 18. The patent is expired, but the same solvent may be covered by later formulation patents.

Is a doxycycline in-situ gel automatically covered by claims 11 or 12?

Not automatically. The formulation would need to satisfy every limitation of the applicable claim, including the claimed polymer, solvent, in-body solidification process, and tetracycline form. The patent is expired in any event.

What is the most important due-diligence issue for a modern competing implant?

The priority issue is identifying unexpired continuation and product-specific patents, then mapping polymer composition, solvent ratio, drug loading, delivery device, release profile, manufacturing process, and approved method of use against those claims.

References

U.S. Food and Drug Administration. (n.d.-a). Atridox doxycycline hyclate label. FDA.

U.S. Food and Drug Administration. (n.d.-b). Approved drug products with therapeutic equivalence evaluations. FDA.

United States Patent and Trademark Office. (1990). U.S. Patent No. 4,938,763, Biodegradable implants and method of producing same. USPTO.

United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights. Office of the Law Revision Counsel.

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Drugs Protected by US Patent 4,938,763

Applicant Tradename Generic Name Dosage NDA Approval Date TE Type RLD RS Patent No. Patent Expiration Product Substance Delist Req. Patented / Exclusive Use Submissiondate
>Applicant >Tradename >Generic Name >Dosage >NDA >Approval Date >TE >Type >RLD >RS >Patent No. >Patent Expiration >Product >Substance >Delist Req. >Patented / Exclusive Use >Submissiondate

International Family Members for US Patent 4,938,763

Country Patent Number Estimated Expiration Supplementary Protection Certificate SPC Country SPC Expiration
European Patent Office 0436667 ⤷  Start Trial 91193 Luxembourg ⤷  Start Trial
European Patent Office 0436667 ⤷  Start Trial C300204 Netherlands ⤷  Start Trial
Austria 151257 ⤷  Start Trial
Austria 162398 ⤷  Start Trial
Austria 228861 ⤷  Start Trial
Australia 2605592 ⤷  Start Trial
Australia 3117493 ⤷  Start Trial
>Country >Patent Number >Estimated Expiration >Supplementary Protection Certificate >SPC Country >SPC Expiration

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